THE PROLACTIN GENE IS EXPRESSED IN THE HYPOTHALAMIC-NEUROHYPOPHYSEAL SYSTEM AND THE PROTEIN IS PROCESSED INTO A 14-KDA FRAGMENT WITH ACTIVITY LIKE 16-KDA PROLACTIN

The 23-kDa form of prolactin (PRL) has been proposed to function as bo th a mature hormone and a prohormone precursor for different uniquely bioactive forms of the molecule. We have shown that the 16-kDa N-termi nal fragment of PRL (16K PRL) inhibits angiogenesis via a specific rec eptor. In addition, 16K PRL stimulates natriuresis and diuresis in the rat, and kidney membranes contain high-affinity specific binding site s for this PRL fragment. 16K PRL can be derived from an enzymatically cleaved form of PRL (cleaved PRL). With the use of a specific 16K PRL antiserum, we have localized a 14-kDa immunoreactive protein in the pa raventricular and supraoptic nuclei of the hypothalamus and in the neu rohypophysis. Reverse transcription-polymerase chain reaction of RNA f rom isolated paraventricular nuclei showed the expression of the full- length PRL mRNA. The neurohypophysis was found to contain the enzymes that produce cleaved PRL, small amounts of PRL, and cleaved PRL. Mediu m conditioned by neurohypophyseal cultures, enriched with the 14-kDa i mmunoreactive protein, has antiangiogenic effects that are blocked by the 16K PRL antiserum. These results are consistent with the expressio n of PRL in the hypothalamic-neurohypophyseal system, and the preferen tial processing of the protein into a 14-kDa fragment with biological and immunological properties of 16K PRL.